PubMed Health⌕ Search

Biomedical subjects

M R Milner

Publications and source records attributed to M R Milner.

At least 19 recordsLinked to original sources
PubMed2000

Insulin increases leptin mRNA expression in abdominal subcutaneous adipose tissue in humans.

Insulin regulates expression and production of leptin in rodents but whether this is also true in humans remains unclear. To test the effects of acute hyperinsulinemia on expression of leptin mRNA in humans, percutaneous needle biopsies of abdominal subcutaneous adipose tissue were performed at baseline and immediately following a 200-min two-step hyperinsulinemic-euglycemic glucose clamp in 16 Pima Indians (8M/8F). Leptin mRNA was quantified by reverse transcription, PCR amplification and expressed relative to actin mRNA. Leptin mRNA levels were higher in women than men (25.6 +/- 1.7 v 16.9 +/- 2.1 relative units, P = 0.003) at baseline. Baseline levels were directly related to percentage body fat (r = 0.54, P = 0. 03) and fasting plasma glucose concentrations (r = 0.57, P = 0.02) and were negatively correlated to glucose disposal at physiologic insulin concentrations (750 +/- 40 pmol/L) during the clamp (r = -0. 51, P = 0.04). Acute hyperinsulinemia (final insulin concentration 11560 +/- 950 pmol/L) increased leptin mRNA levels in 13 of 16 individuals an average of 13% (21.3 +/- 1.7 to 24.2 +/- 1.2 relative units, P = 0.01). Changes in leptin mRNA were directly related to glucose disposal rates during physiologic hyperinsulinemia (r = 0.54, P < 0.04). These results suggest that the expression of leptin mRNA is regulated by insulin in humans, as it is in rodents.

Abdomen↗
PubMed1999

Visceral adipose tissue is not increased in Pima Indians compared with equally obese Caucasians and is not related to insulin action or secretion.

Pima Indians are insulin resistant and hyperinsulinaemic compared with Caucasians. We investigated whether abdominal fat distribution was different between Pimas and Caucasians and whether differences in the amount of visceral fat explained metabolic differences between the groups. Total body fat (absorptiometry) and abdominal fat distribution at L4-L5 (magnetic resonance imaging) were compared in 20 Pima Indians (10 men/10 women) and 20 age-, sex- and BMI-matched Caucasians. Insulin action was measured as glucose disposal during a two-step hyperinsulinaemic-euglycaemic glucose clamp and insulin secretion was assessed in response to oral and intravenous glucose tolerance tests. By design, percent body fat was similar in Pimas and Caucasians. Abdominal visceral and subcutaneous adipose tissue areas were also similar in the two groups (151+/-16 vs 139+/-15 cm2 and 489+/-61 vs 441+/-7 cm2 respectively). Plasma insulin concentrations were higher in Pimas than Caucasians in the fasting state (27+/-6 vs 11+/-2 mU/ml; p < 0.01) and after a 75-g oral glucose load (area under the curve 19975+/-2626 vs 9293+/-1847 mU x l(-1) x 180 min(-1); p < 0.005). Glucose disposal was lower in Pimas than Caucasians during both steps of the clamp and negatively correlated (after adjustment for percent body fat and sex) with visceral adipose tissue in Caucasians (partial r = -0.51, p = 0.03), but not in Pima Indians (r = -0.03, p = 0.92). Insulin secretion was not related to visceral fat independently of percent body fat in either group. We conclude that a relative increase in visceral fat does not explain insulin resistance and hyperinsulinaemia in Pima Indians.

Adipose Tissue↗
PubMed1997

Skeletal muscle triglyceride levels are inversely related to insulin action.

In animal studies, increased amounts of triglyceride associated with skeletal muscle (mTG) correlate with reduced skeletal muscle and whole body insulin action. The aim of this study was to test this relationship in humans. Subjects were 38 nondiabetic male Pima Indians (mean age 28 +/- 1 years). Insulin sensitivity at physiological (M) and supraphysiological (MZ) insulin levels was assessed by the euglycemic clamp. Lipid and carbohydrate oxidation were determined by indirect calorimetry before and during insulin administration. mTG was determined in vastus lateralis muscles obtained by percutaneous biopsy. Percentage of body fat (mean 29 +/- 1%, range 14-44%) was measured by underwater weighing. In simple regressions, negative relationships were found between mTG (mean 5.4 +/- 0.3 micromol/g, range 1.3-1.9 micromol/g) and log10M (r = -0.53, P < or = 0.001), MZ (r = -0.44, P = 0.006), and nonoxidative glucose disposal (r = -0.48 and -0.47 at physiological and supraphysiological insulin levels, respectively, both P = 0.005) but not glucose or lipid oxidation. mTG was not related to any measure of adiposity. In multiple regressions, measures of insulin resistance (log10M, MZ, log10[fasting insulin]) were significantly related to mTG independent of all measures of obesity (percentage of body fat, BMI, waist-to-thigh ratio). In turn, all measures of obesity were related to the insulin resistance measures independent of mTG. The obesity measures and mTG accounted for similar proportions of the variance in insulin resistance in these relationships. The results suggest that in this human population, as in animal models, skeletal muscle insulin sensitivity is strongly influenced by local supplies of triglycerides, as well as by remote depots and circulating lipids. The mechanism(s) underlying the relationship between mTG and insulin action on skeletal muscle glycogen synthesis may be central to an understanding of insulin resistance.

Adult↗
PubMed1996

Interrelationships between muscle morphology, insulin action, and adiposity.

There is evidence that insulin resistance and obesity are associated with relative increases in the proportion of glycolytic type IIb muscle fibers and decreases in the proportion of oxidative type I fibers. Futhermore, insulin resistance and obesity are associated with the fatty acid (FA) profile of structural membrane lipids. The present study was undertaken to define interrelationships between muscle fiber type and oxidative capacity, muscle membrane FA composition, and insulin action and obesity. Muscle morphology, insulin action, and body fat content were measured in 48 male nondiabetic Pima Indians. Percent body fat (pFAT, determined by hydrodensitometry) correlated negatively with percentage of type I fibers (r = -0.44, P = 0.002) and positively with percentage of type IIb fibers (r = 0.40, P = 0.005). Consistent with this finding, pFAT was also significantly related to oxidative capacity of muscle, as assessed by NADH staining (r = -0.47, P = 0.0007) and citrate synthase (CS) activity (r = -0.43, P = 0.008). Insulin action was correlated with oxidative capacity (CS; r = 0.41, P = 0.01) and weakly correlated with percentage of type IIb fibers (r = -0.29, P = 0.05). In addition, relationships were shown between muscle fiber type and FA composition (e.g., percentage of type I fibers related to n-3 FA; r = 0.37, P = 0.01). Thus leaness and insulin sensitivity are associated with increased oxidative capacity and unsaturation of membranes in skeletal muscle. Present studies support the hypothesis that muscle oxidative capacity and fiber type may play a genetically determined or an environmentally modified role in development of obesity and insulin resistance.

Adipose Tissue↗
PubMed1995

Skeletal muscle membrane lipid composition is related to adiposity and insulin action.

The cellular basis of insulin resistance is still unknown; however, relationships have been demonstrated between insulin action in muscle and the fatty acid profile of the major membrane structural lipid (phospholipid). The present study aimed to further investigate the hypothesis that insulin action and adiposity are associated with changes in the structural lipid composition of the cell. In 52 adult male Pima Indians, insulin action (euglycemic clamp), percentage body fat (pFAT; underwater weighing), and muscle phospholipid fatty acid composition (percutaneous biopsy of vastus lateralis) were determined. Insulin action (high-dose clamp; MZ) correlated with composite measures of membrane unsaturation (% C20-22 polyunsaturated fatty acids [r= 0.463, P < 0.001], unsaturation index [r= -0.369, P < 0.01]), a number of individual fatty acids and with delta5 desaturase activity (r= 0.451, P < 0.001). pFAT (range 14-53%) correlated with a number of individual fatty acids and delta5 desaturase activity (r= -0.610, P < 0.0001). Indices of elongase activity (r= -0.467, P < 0.001), and delta9 desaturase activity (r= 0.332, P < 0.05) were also related to pFAT but not insulin action. The results demonstrate that delta5 desaturase activity is independently related to both insulin resistance and obesity. While determining the mechanisms underlying this relationship is important for future investigations, strategies aimed at restoring "normal" enzyme activities, and membrane unsaturation, may have therapeutic importance in the "syndromes of insulin resistance."

Adipose Tissue↗
PubMed1993

Late outcome and quality of life following percutaneous transluminal coronary angioplasty in octogenarians.

Limited data are available concerning the long-term survival and quality of life of octogenarians treated with percutaneous transluminal coronary angioplasty (PTCA). We retrospectively compared the results of PTCA in 118 octogenarians to that of 500 younger subjects. Among the octogenarians, long term follow-up was obtained including survival, relief of angina, assessment of quality of life, and capacity for independent living. These results were compared between men and women. The clinical success rate was 93% for the octogenarians and 88% for the younger patients (p = NS). The lesion success rates were 89% and 88% for these groups, respectively. Results of multilesion PTCA and dilatation of coronary occlusions were similar in both age groups. Major complication rates were 5.9% for the elderly and 3.8% for the younger patients (p < .008). Hospital mortality was higher among the octogenarians (4.6% vs 0.2%, p < .05). Among long-term octogenarian survivors, > 90% indicated a high level of satisfaction with their quality of life and health status. If needed, 88% would undergo the procedure again. Independent living was possible for 66% of these patients and automobile driving for 55%. Octogenarian men and women had similar baseline clinical characteristics, procedural success, complications, relief of angina, and survival. Women indicated a slightly lower level of satisfaction and capacity for independent living. PTCA can achieve a success rate in octogenarians comparable to that of younger patients but with an increased risk of serious complications. Patient satisfaction remains high and a majority of octogenarians remain physically active and capable of independent living.

Activities of Daily Living↗
PubMed1991

Ventricular late potentials in myotonic dystrophy.

OBJECTIVE: To determine the prevalence of ventricular late potentials, as determined by signal-averaged electrocardiography, in patients with myotonic dystrophy. DESIGN: Cross sectional, with blinded analysis of all electrocardiographic data. SETTING: Outpatient departments of a Veterans Affairs medical center and a tertiary care private hospital. PARTICIPANTS: Twenty-four patients with myotonic dystrophy. Patients were excluded from the study if they had either a history suggestive of significant ventricular arrhythmias or electrocardiographic evidence of a bundle-branch block. Two comparison groups were also formed; one group included 44 healthy employees at the tertiary hospital and the other, 30 cardiac patients with inducible ventricular tachycardia. MAIN RESULTS: A time-domain analysis of the signal-averaged electrocardiograms showed that 75% of patients with myotonic dystrophy met one criterion for the presence of late potentials, 67% met two criteria, and 29% met all three criteria. Spectrotemporal mapping in these patients showed markedly abnormal spectral peaks with a mean factor of normality that was significantly lower than that of the normal volunteers; the frequency of electrocardiographic abnormalities approached that seen in patients with known ventricular tachycardia. The presence of late potentials correlated directly with the length of the PR interval and inversely with left ventricular fractional shortening. CONCLUSIONS: In our study, the prevalence of late potentials on signal-averaged electrocardiography in patients with myotonic dystrophy approached that seen in cardiac patients with inducible ventricular tachycardia. It is possible that ventricular arrhythmias play a role in the occurrence of sudden death in some patients with myotonic dystrophy.

Adult↗
PubMed1991

Myotonic heart disease: a clinical follow-up.

We followed 37 patients with myotonic dystrophy for a mean of 6 years. Two developed atrial flutter or fibrillation, 6 developed a new bundle branch block, 1 developed complete heart block requiring a pacemaker, and another with progressive 1st-degree heart block and a widening QRS interval had a sudden death. Most patients had predictable, gradually progressive disease of their cardiac conduction system. We recommend that patients with progressive atrioventricular block or widening QRS interval due to myotonic heart disease have yearly ECGs and be questioned about syncope or presyncope to determine the need for a cardiac pacemaker.

Adolescent↗
PubMed1990

Gonococcal pericarditis with tamponade in a patient with systemic lupus erythematosus.

Pericarditis is one of the most frequent manifestations of systemic lupus erythematosus; however, purulent pericarditis and tamponade are rare. We describe a patient with systemic lupus erythematosus and culture-proven gonococcal arthritis who developed purulent pericarditis with intracellular gram-negative diplococci. Evidence of tamponade was seen on echocardiography. There has not been a reported case of Neisseria gonorrhoeae in pericardial fluid or tissue since the introduction of antibiotics.

Adult↗
PubMed1990

Double-blind crossover trial of diltiazem versus propranolol in the management of thyrotoxic symptoms.

We compared the efficacy of diltiazem and propranolol in a randomized, prospective, double-blind, crossover study in six patients with untreated thyrotoxicosis (mean age 31 yrs). The patients received either diltiazem 60 mg orally four times a day or propranolol 40 mg orally four times a day, each for 1 week, separated by a 3-day drug-free period. Blood pressure, heart rate, thyroid hormone levels (free T4, T3), electrocardiogram, two-dimensional and M-mode echocardiograms, and Doppler studies were performed. In addition, 8 clinical signs and 18 symptoms of thyrotoxicosis were graded. All subjects felt better with drug therapy, with three preferring diltiazem to propranolol. No significant difference in clinical response or in hemodynamic effects was noted between the agents. These data suggest that diltiazem may serve as an alternative therapy for beta blockers in controlling thyrotoxic symptoms in patients in whom beta blockade may be contraindicated.

Administration, Oral↗
PubMed1989

Usefulness of fish oil supplements in preventing clinical evidence of restenosis after percutaneous transluminal coronary angioplasty.

This study assesses the effect of dietary supplements with high dose omega-3 fatty acid (N3FA) on the frequency of clinical restenosis during the 6 months after successful percutaneous transluminal coronary angioplasty (PTCA). One hundred ninety-four patients (214 significant coronary narrowings) were randomized after successful PTCA to receive conventional medical therapy or to an identical regimen supplemented by high dose N3FA (4.5 g/day). Enrollment required angina pectoris and successful dilatation of all significant coronary narrowings. The subjects were randomly assigned to either no N3FA (control, n = 99) or N3FA supplementation (n = 95). After a 1-week trial period, 11 (group 2) declined further treatment because of side effects. The remaining 84 subjects (group 1) continued N3FA throughout the 6-month period. Monthly clinical follow-up was obtained in all patients. Ninety-two percent of patients had cardiac testing for evaluation of recurrent ischemia. Except for a greater percentage of women in the group refusing N3FA supplementation (group 2), the 3 groups were similar in demographic data, medical history, dietary habits, history of previous PTCA and angiographic characteristics. Of the 194 subjects, 56 had clinical restenosis (45 by cardiac catheterization, 8 by exercise testing and 3 by symptoms alone [refused further clinical testing]). Reocclusion rates were: group 1 19%, group 2 46%, and control 35%. Analysis both in accordance with the principle of intention to treat and for subjects who actually received N3FA revealed a significant effect of N3FA on preventing clinical restenosis (p less than 0.04 and p = 0.008, respectively). These data suggest that high dose N3FA supplements reduce the clinical restenosis rate after successful PTCA.

Angiography↗
PubMed1989

Left ventricular filling patterns in aortic stenosis in patients older than 65 years of age.

Left ventricular (LV) filling patterns in 26 elderly (mean age 81 years) patients with severe aortic stenosis (AS) were evaluated using pulsed-wave Doppler echocardiography. Parameters of LV filling, including the ratio of the peak atrial velocity to the peak early diastolic velocity (A/E ratio) and the percent contribution of active atrial filling to total LV filling (%A), of these patients with AS (group I) were compared with 2 groups presumed to have abnormal LV filling: elderly patients (group II) and hypertensives with increased LV mass (group III), as well as with normal volunteers (group IV). The patients with AS had a broad range of LV inflow velocity patterns (A/E = 0.91 +/- 0.56, range 0.20 to 1.91; %A = 34.3 +/- 16.4, range 3.0 to 65), as compared with the consistently low A/E ratio (0.48 +/- 0.13) and %A (25 +/- 7) in the normal volunteers and the high A/E ratio and %A in the elderly (A/E = 1.48 +/- 0.28, %A = 49 +/- 11) and hypertensive (A/E = 1.41 +/- 0.32, %A = 49 +/- 8) groups. When comparing the data obtained by Doppler with hemodynamics at catheterization, the patients with AS and a high A/E ratio (A/E ratio greater than 1, n = 11) had lower LV mid-diastolic pressures (7 vs 18 mm Hg, p less than 0.001), lower pulmonary artery systolic pressures (33 vs 49 mm Hg, p less than 0.05) and less symptomatic heart failure than those patients with AS and a low A/E ratio (A/E less than 1). The aortic valve area was similar in these 2 subgroups (0.40 vs 0.37 cm2).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

The application of radionuclide ventriculography to cardiac screening.

Screening asymptomatic individuals for latent coronary disease often requires sequential testing because exercise electrocardiography typically produces more false positive than true positive results in a population with a low prevalence of coronary disease. Cardiac scintigraphy is a technique that may be employed as a confirmatory test in lieu of coronary arteriography to further evaluate the significance of a positive exercise electrocardiogram. Radionuclide ventriculography was employed in 98 asymptomatic individuals who were considered to be at moderate risk of heart disease after risk factor analysis and exercise electrocardiography. Seventeen (17%) patients had an abnormal study and underwent cardiac catheterization. Seven had coronary artery disease, two had cardiomyopathy, and eight were normal. Eighty-one (83%) patients had a normal study. Because the sensitivity of radionuclide ventriculography is 63-80%, it was postulated that 2 to 5 individuals with disease were missed. Thus, from a population with an 11-14% prevalence of disease, two subsets were identified. A large subset in which a prevalence of 2-6% could be estimated was separated from a much smaller one in which a prevalence of approximately 50% was demonstrated.

Adult↗
PubMed1988

Heart rate adjustment of ST-segment depression for reduction of false positive electrocardiographic responses to exercise in asymptomatic men screened for coronary artery disease.

The ability of heart rate (HR) correction of exercise-induced ST-segment depression (the delta ST/HR index) to reduce the number of false positive exercise electrocardiograms during initial screening for occult coronary artery disease (CAD) was examined in active, asymptomatic men from the Army Reserve. Among 606 consecutive men given treadmill tests, 62 asymptomatic subjects with normal results on resting electrocardiograms but abnormal outcomes on standard exercise electrocardiograms underwent rest and exercise radionuclide cineangiography, and the 10 subjects with abnormal radionuclide findings then underwent coronary angiography. A previously established delta ST/HR index less than 1.6 microV/beat/min correctly identified 34 of 52 subjects (65%) who, despite abnormal standard exercise electrocardiographic findings, had no rest or exercise radionuclide abnormalities. A delta ST/HR index greater than or equal to 1.6 microV/beta/min detected 7 of 7 subjects with abnormal radionuclide cineangiograms who had CAD at cardiac catheterization, but also identified 2 of 3 subjects with an abnormal radionuclide test who had no CAD. In contrast to the 7 of 62 subjects (11%) with abnormal standard exercise test criteria who had radionuclide and angiographic evidence of CAD, a delta ST/HR index partition of 1.6 microV/beat/min separated subjects into subgroups with 0% (0 of 35) vs 26% (7 of 27) prevalences of CAD by serial diagnostic evaluation (p less than 0.01). Thus, among asymptomatic subjects with abnormal electrocardiographic responses to exercise, simple HR correction of the magnitude of ST-segment depression reduced by 56% the number of subjects with standard exercise test criteria leading to referral for additional diagnostic evaluation, without loss of sensitivity for angiographically proven CAD and with accurate negative predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Angiography↗